Anaplastic astroblastoma of childhood: aggressive behavior.

OBJECTIVE: Astroblastoma is an unusual brain tumor in childhood. Tumor usually arises from cerebral hemispheres. This large tumor is well-demarcated, lobulated, solid or cystic, and therefore, may resemble glioblastoma. Histopathologically, there are two types of astroblastoma: well-differentiated (low-grade) or anaplastic (high-grade). In low-grade astroblastoma, treatment of choice is complete excision. This type of tumor usually does not recur. However, anaplastic tumors can recur despite surgery, radiation, and chemotherapy and may be problematic for clinician. CASE REPORT: A 7-year-old female patient presented with an acute onset of vomiting and seizure. Magnetic resonance imaging study revealed a large mass in the left parieto-occipital region. She underwent total excision of the tumor. Histopathologically, the tumor was an anaplastic astroblastoma. Her adjuvant treatment was planned to consist of radiation therapy and cisplatin-based chemotherapy. However, the tumor recurred early in the course, and she died 18 months after diagnosis. CONCLUSION: High-grade astroblastomas behave like glioblastoma, as emphasized in this case report. Local control of this type of tumor seems difficult despite surgery, radiation therapy, and cisplatin-based chemotherapy.

A single institutional experience: is epoetin alpha effective in anemic children with cancer?

The authors aimed to investigate the efficacy of epoetin-alpha on hemoglobin levels and red cell transfusion requirement in children with both hematologic malignancy (HM, n = 27) and solid tumors (ST, n = 14). Epoetin-alpha was given (150 U/kg or 250 U/kg, thrice weekly) for 12 weeks. Epoetin alpha significantly increased the hemoglobin levels at the 2nd and 3rd months of therapy (p <.05). At the 3rd month, the patients required less red cell transfusion. At the dose of 150 U/kg, only three patients with HM, but none of the ST patients, required red cell. However, none required red cell transfusion after 2nd month on epoetin alpha 250 U/kg. Epoetin-alpha administration increases hemoglobin levels and decreases red cell transfusion requirement in children with malignancy.

Histopathologic and Immunophenotypic Features of Childhood and Adult Anaplastic Large-Cell Lymphomas.

The t (2;5) (p23; q35) translocation associated with CD30-positive anaplastic large-cell lymphoma (ALCL) creates a hybrid gene encoding the chimeric nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NFMALK) protein, which can be demonstrated by immunostaining with ALK1 monoclonal antibody. In this study, 40 specimens of ALCL from 6 pediatric, 34 adult patients, were immunostained with monoclonal antibodies against CD30 (Ber-H2), EMA, CD45 (LCA), CD3, CD20 (L26), CD15, and ALK1 antigens, and results were correlated with histopathologic features. The mean age of the pediatric and adult patients was 10-years and 38-years, respectively. ALK1 was positive in 14 cases (35%) representing 83% of pediatric and 26% of adult patients, statistically significantly higher in the pediatric group (p= 0.01). Considering the better prognosis attributed to cases with t (2;5), it is interesting to note that the percentage of ALK1-positive cases is significantly higher in pediatric patients with coexpression of EMA, compared to adults.

Plasma concentrations of granulocyte-macrophage colony-stimulating factor and interleukin-6 in septic and healthy preterms.

UNLABELLED: Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) concentrations were determined in 21 preterm infants with sepsis and nine healthy preterm neonates of the same postnatal age at sampling. Plasma GM-CSF levels were elevated at diagnosis in the septic preterms as compared to the healthy preterms (P = 0.01), but did not differ significantly on recovery. IL-6 levels were also elevated markedly at diagnosis (P = 0.0003), but decreased to normal on recovery as compared to the healthy preterm infants. GM-CSF levels were more prominent in septic preterms with neutropenia than those of non-neutropenic infants (P = 0.03). CONCLUSION: Preterm infants can produce high levels of granulocyte-macrophage colony-stimulating factor and interleukin-6 in response to bacterial sepsis.

The role of 99Tcm-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: comparison with 131I-MIBG and 99Tcm-MDP scintigraphy.

In this study, we investigated prospectively the diagnostic role of 99Tcm-MIBI for staging and for predicting the therapeutic response of stage IV neuroblastoma compared with 131I-MIBG imaging and 99Tcm-MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with 99Tcm-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg-1 99Tcm-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with 131I-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by 131I-MIBG scintigraphy. None of the primary lesions demonstrated significant 99Tcm-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 131I-MIBI-avid neuroblastoma metastases that were 99Tcm-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were 99Tcm-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for 131I-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate 99Tcm-MIBI. Clinical evaluation of patients with no 99Tcm-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. All 99Tcm-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that 99Tcm-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy.

Urinary zinc excretion and zinc status of patients with beta-thalassemia major.

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (micromol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.

Sequential use of deferiprone and desferrioxamine in primary school children with thalassaemia major in Turkey.

The effectiveness of the sequential use of deferiprone and desferrioxamine (DFO) in children with thalassaemia major was examined. Seven thalassaemic children in whom urinary iron induced by deferiprone was sufficient to maintain a negative iron balance were enrolled in the long-term trial. Deferiprone at a dose of 75 mg/kd/day in 3 divided doses was given for 4 school days a week. The group was given DFO at a dose of 40-50 mg/kg/day s.c. over 8-12 h with a battery-operated pump for 2 days at the weekend. In addition to the safety variables, they were monitored for serum ferritin levels at 2-month intervals and hepatic iron concentrations in liver tissues were determined at the beginning and the 6th month of therapy. The severity of hepatic damage was graded according to the Knodell hepatic activity index and the fibrosis was quantified. None of the patients suffered adverse effects of the therapy but a transient increase in serum ALT levels was noted. A nonsignificant decline in serum ferritin was observed (p = 0.08), a significant reduction in hepatic iron concentration was also determined (p = 0. 03). The hepatic activity index in liver tissues of the patients at the 6th month of the sequential therapy significantly decreased (p = 0.03) whereas fibrosis scores did not differ significantly (p = 0. 25).

Neuropsychologic sequelae in the long-term survivors of childhood acute lymphoblastic leukemia.

The neurotoxicity of either systemic chemotherapy or central nervous system prophylaxis was studied in 19 children treated for acute lymphoblastic leukemia (ALL). They had completed ALL therapy at least a year before and survived more than 5 years after diagnosis. The duration between age at diagnosis and age at investigation was 8.6 +/- 2.7 years (5-15 years). Neuropsychologic tests, cranial magnetic resonance imaging (MRI), and evoked potentials (EP) were studied. Seventeen healthy siblings were taken as a control group. Emotional evaluation was done using the childhood depression inventory and Beck depression inventory. Cognitive functions were evaluated using Wechsler's Intelligence Scale for Children-Revised (WISC-R) or the Wechsler's Adult Intelligence Scale-Revised (WAIS-R) tests, which were adapted to Turkish children. Performance and total IQ scores (94.0 +/- 16.8 and 92.2 +/- 16.5) were significantly low as compared to the control group (112.1 +/- 18.9 and 105.4 +/- 14.2) (p = .007 and p = .02). Abnormal MRI findings were found in 33.3% (6/18). Three out of 18 patients (16.6%) had abnormal auditory while 5 out of 17 patients (29.5%) displayed abnormal visual EPs. Abnormal findings in MRI, cognitive examination, and electrophysiologic testing were not associated with age at diagnosis, radiotherapy doses, intermediate/high-dose systemic methotrexate administration or central nervous system involvement. But more patients must be studied to demonstrate discrete outcomes of neurotoxicity in long-term survivors of childhood leukemia.

Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy.

The aim of this study was to evaluate the value of three-phase dynamic bone scintigraphy (TPBS) in the assessment of the response of bone sarcomas to pre-operative chemotherapy and to correlate serial scintigraphic changes with histological findings. The study group comprised 27 patients (osteogenic sarcoma, n = 20; Ewing's sarcoma, n = 5; malignant fibrous histiocytoma, n = 2) with a mean age of 19.2 years. All patients received 99Tcm-methylene diphosphonate TPBS before and after pre-operative chemotherapy. Each phase of the imaging procedure was interpreted qualitatively and quantitatively. The percentage of tumour necrosis was analysed on resection materials following surgery. Histologically, 12 patients were non-responsive (tumour necrosis less than 90%) and 15 patients were responsive (tumour necrosis more than 90%). A decrease in the tumour blood flow ratio and extension were the most notable findings in the responders. The mean change in the tumour blood flow ratio following therapy was 58.7 +/- 8.3% and 19.9 +/- 26.6% (P < 0.005) in responders and non-responders respectively. The accuracy of three-phase imaging and static bone scintigraphy was 88% and 74% respectively. Since bone scintigraphy is a valuable technique owing to its ability to detect distant metastases in clinically early disease, TPBS should be helpful in monitoring therapy effects without any additional cost or radiation dose.

Histiocytic syndromes in children.

The "histiocytes" are a group of proliferative disorders of the mononuclear phagocyte system whose etiologies are basically unknown. The majority of childhood histiocytoses are expressions of excessive numbers of Langerhans cells, representing so-called Langerhans cell histiocytosis. Fifteen patients who were diagnosed with histiocytosis syndrome at the Pediatric Hematology and Oncology Department of Ege University Hospital between October 1986 and January 1995 were included in this study. The majority of the patients had Langerhans cell histiocytosis (LCH), and skeletal involvement was the most common manifestation. A good response to radiotherapy and chemotherapy was obtained by our patients with unifocal and multifocal involvement of LCH. Two patients with disseminated LCH died with progressive disease. In the patient with Rosal-Dorfman disease, a partial response was obtained with prednisone. The patient with malignant histiocytosis died during a relapse at the end of one year. Organ dysfunction and the patient's age are important factors affecting the outcome of the disease.

Early determination of nutritional problems in pediatric cancer patients.

Mild and marginal malnutrition must be identified to prevent the development of severe protein-energy malnutrition in pediatric cancer patients. We aimed to evaluate nutritional status and determine daily energy, protein and micronutrient intake to identify mild or marginal malnutrition in pediatric cancer patients. Daily energy, protein and micronutrient intake, anthropometric measurements and biochemical indices were studied in 45 patients (25 in remission, 20 newly diagnosed or relapsed) who consumed energy, protein, vitamins and minerals below the recommended quantities. According to the weight-for-height index, 23 children (51.1%) were determined to be malnourished. Absolute and relative prealbumin values were 19.4 +/- 7.2 mg/dl and 74.3 +/- 29.1 mg/dl in the remission group, and 14.8 +/- 5.1 mg/dl and 58.1 +/- 23.3 in the active disease group, respectively (p < 0.05). Relative prealbumin values were found to be low in 63.6 percent of nonmalnourished children, and 80 percent of children with mild malnutrition. We conclude that malnutrition is common in pediatric cancer patients, and prealbumin is a reliable and sensitive indicator of mild and marginal malnutrition. Determining prealbumin values and assessing the deficiency of micro- and macronutrients before malnutrition is detected by anthropometric measures may provide a warming that nutritional problems may occur.

Prophylactic therapy for hemophilia in a developing country, Turkey.

Prophylaxis has been practiced for many years in Europe and is gaining acceptance worldwide with current viral inactivation procedures. Unfortunately, the high cost of prophylaxis is currently the major obstacle to its implementation in developing countries such as Turkey. The aim of this controlled preliminary study is to evaluate the efficacy, safety, and feasibility of prophylaxis. Seven boys aged 1.5-7 years (5.0 +/- 1.8), who had severe hemophilia (six A, one B) received 20-50 IU/kg factor twice weekly and were followed up for 6-24 months (14.5 +/- 6.6). Intermediate concentrates have been used in hemophilia A and ultrapure product for hemophilia B. The data obtained for the same group of patients before prophylaxis were used as a control group. Another control group was selected in another group of 10 hemophiliacs, mean age 12.5, and received treatment on demand. During prophylactic treatment, the episodes of bleeding were decreased (from 10.5 +/- 3.2 to 4.5 +/- 3.6). Orthopedic and radiologic joint scores were stable (from 0 to 1 and from 1.1 +/- 1.2 to 1.0 +/- 1.5). The patients spent significantly fewer days in the hospital (from 18 +/- 12 to 0.7 +/- 0.6). None of the patients was infected with hepatitis A, hepatitis B, or human immunodeficiency virus. One patient was seroconverted with anti-hepatitis C virus in the third month of prophylaxis. Mean consumption of concentrates for prophylaxis was 3489 +/- 960 IU/kg per year compared with 2073 +/- 1302 in conventional therapy. Prophylaxis was superior to treatment on demand even when given in a twice-weekly period with intermediate concentrates. In Third World countries, prophylaxis should be tried at least in selected severely hemophilic children in order to prevent disabilities.

Serum erythropoietin levels in patients with beta thalassemia major and intermedia.

Serum erythropoietin (EPO) levels were determined by radioimmunoassay in 37 beta-thalassemia patients, the phenotype being thalassemia major (TM) in 30 and thalassemia intermedia (TI) in 7. The control group consisted of 37 healthy children. The mean serum EPO levels were significantly higher in patients with both TM (215.1 +/- 144.5) and TI (53.8 +/- 40.2) compared with the control group (9.3 +/- 4.6). Although the mean hemoglobin (Hb) concentrations in the patients with TM and TI were similar (8.6 +/- 0.9 and 8.7 +/- 1.1, respectively), the mean serum EPO level was significantly higher in TM patients than the patients with TI (P < .01). This finding may indicate that some other factors contributing to the metabolic adaptation to low oxygen concentration or improvement of the tissue oxygenation are as effective as the Hb concentration in EPO production. It is also suggestive of the fact that some amount of tissue hypoxia cannot be prevented in spite of polytransfusion regimens in TM patients. Serum EPO levels of TM patients were not found to be age related or correlated with the mean pretransfusional Hb levels. In the TM patients, the serum EPO concentration was not consistently correlated with clinical signs of erythropoietic activity. This may be indicative of personal differences with respect to the sensitivities of erythroid precursors to the increasing EPO levels in TM patients.